Efficacy of Adjuvant Mitotane Treatment (ADIUVO)

NCT00777244 | Unknown Phase 3 DMC

• 1 other identifier: EudraCT 2007-007262-38
• Study Type: interventional
• Target: 200
• Locations: 7 countries
• Sites: 28

Brief Summary

Study Rationale Adrenocortical carcinoma (ACC) is a very rare disease with a high risk of relapse after radical surgery. The efficacy of adjuvant mitotane treatment is suggested by a retrospective multicenter international study showing that postoperative mitotane treatment was associated with a significant reduction of the risk of relapse and death. However, these promising results need confirmation in a randomized prospective study. Caution should be adopted particularly in patients with low risk of disease relapse, in whom the benefit of therapy should be weighted against the side effects. Even if an adjuvant treatment seems justified in patients at high risk of relapse, a randomised prospective study is needed to assess whether such a treatment is efficacious in patients at low-intermediate risk. The purpose of the present study is to determine whether adjuvant mitotane treatment is effective in prolonging the disease free survival in patients with adrenocortical carcinoma at low-intermediate risk of progression who underwent radical resection

Conditions

Adrenocortical Carcinoma

Keywords

mitotane; adjuvant therapy; disease free survival

Outcome Measures

Primary Outcomes (1)

• Disease Free survival

  Survival in years

  Till the last follow up

Study Arms (2)

Follow-up

NO INTERVENTION

Arm B

Mitotane

EXPERIMENTAL

Arm A

Drug: MITOTANE

Interventions

MITOTANE DRUG

mitotane will be administered at a starting dose of 1.5 g/day and increased in case of good gastrointestinal tolerance on day 2 to 3 g/day, on day 3 to 4.5 g/day, and on day 4 to 6 g/day. A dose of 6 g/day will be administered until first mitotane blood level is assessed. Further adjustment of dosage will be performed according to blood concentrations and tolerability.

Also known as: Mitotane (Lysodren)

Mitotane

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of ACC according to Weiss system by a national reference pathologist who has to be nominated before study initiation.
• Low-intermediate risk of relapse defined as:
• Stage I-III (according to ENSAT classification 2008; see Appendix 2)
• Microscopically complete resection, defined as no evidence of microscopic residual disease based on surgical reports, histopathology and post-operative imaging. Detailed pathological and surgical reports prepared according to guidelines detailed in appendix x and y should be available for assessment.
• Ki 67 \< 10%
• Post-operative imaging (thoracic and whole abdominal CT with contrast medium or MRI) demonstrating no evidence of disease within 4 weeks from randomization
• Age \> 18 years
• ECOG performance status 0-2 (Appendix 3)
• Adequate bone marrow reserve (neutrophils \> 1000/mm3 and platelets \> 80000/ mm3)
• Ability to comply with the protocol procedures (including geographic accessibility)
• Written informed consent

You may not qualify if:

• Time between primary surgery and randomization \> 3 months.
• Repeat surgery for recurrence of disease
• Presence of autonomous adrenocortical hormone secretion despite the absence of disease detectable with imaging techniques
• History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years
• Renal insufficiency (creatinine clearance \< 40 ml/min) or liver insufficiency (serum bilirubin \> 2 times the upper normal range and/or serum transaminases (AST/SGOT, ALT/SGPT, but not gamma Glutamyl Transpeptidase) \>3 times the upper normal range). Creatinine clearance may be calculated according to validated formulas (Crockoft's or MDRD)
• Pregnancy or breast feeding
• Previous or current treatment with mitotane or other antineoplastic drugs for ACC
• Previous radiotherapy of the tumor bed (for ACC).
• Any other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• University of Turin, Italy: lead

Study Sites (28)

Medical Oncology Branch - Center for Cancer Research - National Cancer Institute

Bethesda, Maryland, 20892-1903, United States

RECRUITING

Endocrine Oncology - University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0921, United States

ACTIVE NOT RECRUITING

Endocrinologie - Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, 3840, Canada

RECRUITING

Endocrinologie - CHU Besançon Hôpital Jean Minjoz

Besançon, 25000, France

RECRUITING

Endocrinologie - CHU Lyon Hôpital Pierre Wertheimer

Bron, 69677, France

RECRUITING

Endocrinologie - Hôpital A. Michallon

La Tronche, 38700, France

RECRUITING

Endocrinologie - Cochin, APHP

Paris, 75679, France

RECRUITING

Endocrinologie - CHU Toulouse Hôpital Larrey

Toulouse, France

RECRUITING

Endocrinologie - Institut de Cancérologie Gustave Roussy

Villejuif, 94805, France

RECRUITING

University Hospital Campus Mitte Charitè, Berlin

Berlin, 10117, Germany

RECRUITING

University Hospital of Dresden

Dresden, 01307, Germany

RECRUITING

University Hospital of Düsseldorf

Düsseldorf, 40001, Germany

NOT YET RECRUITING

Center for Endocrine Tumors - ENDOC

Hamburg, 20357, Germany

RECRUITING

University Medicin Centre of Munchen

München, 80336, Germany

RECRUITING

University Hospital Wuerzburg, Endocrinology

Würzburg, 97080, Germany

RECRUITING

A.O.Universitaria Arcispedale S.Anna Ferrara

Ferrara, Fe, 44100, Italy

RECRUITING

UO Oncologia Medica - AO Spedali Civili

Brescia, 25123, Italy

RECRUITING

Università degli studi di Firenze

Florence, Italy

NOT YET RECRUITING

Azienda Ospedaliera di Foggia

Foggia, Italy

ACTIVE NOT RECRUITING

Ospedale Cà Granda-Niguarda-Milano

Milan, Italy

RECRUITING

Azienda Ospedaliera San Luigi

Orbassano, 10043, Italy

RECRUITING

Department of Clinical and Biological Sciences, University of Turin, Internal Medicine 1

Orbassano, 10043, Italy

RECRUITING

Azienda Ospedaliera Padova

Padua, Italy

ACTIVE NOT RECRUITING

Università degli studi di Palermo

Palermo, Italy

NOT YET RECRUITING

Policlinico Universitario A. Gemelli

Roma, Italy

ACTIVE NOT RECRUITING

A.O.U. San Giovanni Battista - Molinette

Torino, Italy

RECRUITING

Dept. of Internal Medicine Maxima Medisch Centrum

Eindhoven, 5600 PD, Netherlands

RECRUITING

Cancer Research UK Clinical Trials Unit (CRCTU) - School of Cancer Sciences - University of Birmingham

Birmingham, Edgbaston, 152TT, United Kingdom

NOT YET RECRUITING

Related Publications (2)

• Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, Rossetto R, Buci L, Sperone P, Grossrubatscher E, Reimondo G, Bollito E, Papotti M, Saeger W, Hahner S, Koschker AC, Arvat E, Ambrosi B, Loli P, Lombardi G, Mannelli M, Bruzzi P, Mantero F, Allolio B, Dogliotti L, Berruti A. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med. 2007 Jun 7;356(23):2372-80. doi: 10.1056/NEJMoa063360.

  PMID: 17554118 BACKGROUND

• Terzolo M, Fassnacht M, Perotti P, Libe R, Kastelan D, Lacroix A, Arlt W, Haak HR, Loli P, Decoudier B, Lasolle H, Quinkler M, Haissaguerre M, Chabre O, Caron P, Stigliano A, Giordano R, Zatelli MC, Bancos I, Fragoso MCBV, Canu L, Luconi M, Puglisi S, Basile V, Reimondo G, Kroiss M, Megerle F, Hahner S, Kimpel O, Dusek T, Nolting S, Bourdeau I, Chortis V, Ettaieb MH, Cosentini D, Grisanti S, Baudin E, Berchialla P, Bovis F, Sormani MP, Bruzzi P, Beuschlein F, Bertherat J, Berruti A. Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study. Lancet Diabetes Endocrinol. 2023 Oct;11(10):720-730. doi: 10.1016/S2213-8587(23)00193-6. Epub 2023 Aug 21.

  PMID: 37619579 DERIVED

Related Links

• study website

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

Mitotane

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals

Study Officials

• Massimo Terzolo, MD

  Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Italy

  STUDY CHAIR

• Martin Fassnacht, MD

  Department of Internal Medicine, University of Wuerzburg, Germany

  STUDY DIRECTOR

• Alfredo Berruti, MD

  Medical Oncology, Department of Clinical and Biological Sciences, University of Turin

  STUDY CHAIR

• Eric Baudin, MD

  Oncologie Endocrinienne et Médecine Nucléaire, Institut Gustave Roussy, Villejuif, France.

  PRINCIPAL INVESTIGATOR

• Harm Haak, MD

  Department of Internal Medicine, Máxima Medical Centre, Eindhoven, The Netherlands

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paola Perotti

CONTACT

+390119026; oncotrial.sanluigi@gmail.com

Paola Sperone

CONTACT

+390119026; paola.sperone@email.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: October 21, 2008
• First Posted: October 22, 2008
• Study Start: April 1, 2008
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2020
• Last Updated: May 8, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (6); US (2); IT (11); NL (1); GB (1); FR (6); CA (1)